1,2-Amino-oxy arenes, such as o-aminophenols, and related nitrogen-containing heterocycles with aromatic C—N bonds are ubiquitous moieties in pharmaceutical, agrochemical and materials sciences, where they impart desirable and essential properties to small molecules as well as macromolecules. Examples of 1,2-amino-oxy arenes include:
(The aromatic C—O and C—N bonds of the arene are in bold.)
However, despite its importance to the function of organic molecules, nitrogen is not present in petrochemical building blocks. These starting materials possess high ratios of hydrogen to carbon, making the selective oxidation of C—H bonds critically important to laboratory and industrial chemical synthesis. In fact, the site-selective introduction of nitrogen, in particular, the amination of aromatic rings, is fundamentally important to the petrochemical industry, since it dictates the efficiency of feedstock valorization.
Modern technologies to introduce nitrogen are dominated by metal-catalyzed cross-coupling reactions, where the most desirable examples introduce aromatic C—N bonds directly from aromatic C—H bonds and un-functionalized amines. These so-called Crossed Dehydrogenative Coupling (CDC) reactions are efficient because they combine un-functionalized starting materials. However, their poor chemoselectivity, regioselectivity, and their poor atom economy remain persistent drawbacks.
Improving the synthesis of ortho-amino-phenols and their 1,2-oxy-amino derivatives is a fundamentally important challenge, since this motif is found in pharmacologically active compounds, chemical dyes, agrochemicals, and catalysts (see above). However, their synthesis involves a non-regioselective nitration of phenols, followed by multi-step syntheses that involves protecting group strategies for further derivatization. Fragment-coupling reactions of halogenated arenes with nitrogen or oxygen nucleophiles can be preferable, but requires pre-functionalization of the arene, and catalyst optimization for a given heteroatom nucleophile. Thus, a more direct functionalization of aromatic C—H bonds is desirable, but currently suffers from limited scope, and requires pre-functionalization of the nitrogen coupling partner or stoichiometric quantities of an oxidant.
Azophenols are also important scaffold and are present in organic dyes, ancillary ligands, molecular switches, fluorescent probes and chemosensors. Here are selected examples of azophenol derivatives:

Azophenols display unusually rapid cis-to-trans thermal relaxation, and the rate of this isomerization is influenced by the electronic properties of each of the arene rings. For example, the thermal isomerization of azophenols with push-pull configuration (i.e. with an adjacent electron-deficient arene) are amongst the fastest. Despite their utility, efficient synthesis to access this core system is limited, and a catalytic aerobic method has not been reported. Traditionally, azophenol is generated from the fragment coupling of aryl diazonium salt and phenol. However, this coupling requires in situ preparation of diazonium salts, which is obtained from the oxidation of the corresponding aniline with stoichiometric amounts of toxic nitrous acid.
Transition metal catalyzed ortho-functionalization of symmetric azobenzenes have been proposed. However, these protocols provide a mixture of mono- and di-hydroxylated products, and produces azoxybenzene byproducts. Consequently, the use of these methodologies on asymmetric substrates can give rise to complex product mixtures, and predicting the site of hydroxylation can be difficult for substrates with electronically and sterically comparable arene rings. Thus, a general, regioselective and aerobic catalytic method for the synthesis of azophenol would be highly attractive.